Development of CpG oligodeoxynucleotide TLR9 agonists in anti-cancer therapy

ABSTRACT

Introduction: Toll-like receptor-9(TLR9) can recognize the foreign unmethylated CpG DNA, and thus intrigue a strong Th1 response which plays a crucial role in the innate and adaptive immune responses. To date, CpG oligodeoxynucleotide (ODN)-based TLR9 agonists have undergone four generations. Each generations’ breakthroughs in immune activation, safety profiles and pharmacokinetic properties were confirmed by both preclinical and clinical studies.

Areas covered: We reviewed the development and major clinical trials of TLR9 agonists and summarized the optimization strategies of each generation. The applications, limitations and prospects of TLR9 agonists in cancer immunotherapy are also discussed.

Expert opinion: Clinical trials of CpG ODN TLR9 agonists as a single agent demonstrated insufficient e…